Significance The proposed studies will investigate the aged macaque as the model for human menopausal transition. Objectives By use of endocrine assay systems that evaluate ovarian function, previous studies on women in the perimenopausal transition can be compared to that employed in primates. In addition, obtaining data from hormonal interventions on macaques, will give directly comparable data to that obtained in humans. In the first phase of the study, 20 aged females between 18 and 26 years have had daily urines and twice monthly blood collections obtained for one year in order to assess ovarian function. In addition, a group of ten normal cycling adult macaques had daily urines and twice monthly blood samples collected for comparison to the aged macaques. In order to complete the hormone intervention phases of the study, a dose response using intramuscular injections of estradiol cypionate at 5, 10 and 20 5g/ml were administered to three macaques selected from the group of twenty aged macaques. Results Urinary E1C and PdG were assessed in the twenty aged macaques along with menstrual calendar data for each animal. These data were collated and used to classify the animals into either anovulatory, normal or abnormal cycling groups. There were 7 anovulatory, 3 with abnormal cycles, 1 with short follicular and long luteal phases, 1 with short cycles and 8 with normal cycles. In the anovulatory group, maximum levels of E1C and PdG ranged from 55 to 261 ng/mgCr and 130 to 2865 ng/mgCR respectively. In the normal cycling group, maximum levels of E1C and PdG ranged from 116 to 472 ng/mgCr and 874 to 4886 ng/mgCR respectively. Future Directions Hormone replacement studies will be conducted to create changes that are similar to normal hormonal fluctuations, in turn allowing for further understanding of the menopausal transition. KEY WORDS hormone replacement, menopause, ovarian senescence FUNDING NIH Grant 96-023